title: A novel rodent model that mimics the metabolic sequelae of obese craniopharyngioma patients.
abstract: Patients with craniopharyngioma (CP), a tumor located in the pituitary and/or hypothalamus, are susceptible to developing obesity and many metabolic complications. The study aim was to create a rodent model that mimics the complex neuroanatomical and metabolic disturbances commonly seen in obese CP patients. We compared the metabolic phenotype of animals with three distinct types of hypothalamic lesions: 1) destruction of the arcuate nucleus (ARC) induced by monosodium glutamate (MSG), 2) electrolytic lesion of the adjacent ventromedial nucleus (VMN) alone, 3) both the VMN and dorsomedial nucleus (DMN), or a 4) combined medial hypothalamic lesion (CMHL) affecting the VMN, DMN, and the ARC. Only the CMHL model exhibited all key features observed in patients with hypothalamic obesity induced by CP. These features included excessive weight gain due to increased adiposity, increased food intake, and pronounced hyperinsulinemia and hyperleptinemia. Similar to characteristics of patients with CP, CMHL animals exhibited reduced plasma levels of alpha-melanocyte stimulating hormone and reduced ambulatory activity compared with weight-matched controls. Therefore, the CMHL model best mimics the complex metabolic abnormalities observed in obese CP patients compared with lesions to other hypothalamic areas and provides a foundation for future pharmacological approaches to treat obesity in children with hypothalamic damage.
authors.affiliation: Division of Endocrinology, Seattle Children's Research Institute, University of Washington, Seattle, Washington 98101, USA. christian.roth@seattlechildrens.org
authors.forename: Christian L
authors.initials: CL
authors.lastname: Roth
authors.forename: James E
authors.initials: JE
authors.lastname: Blevins
authors.forename: Melissa
authors.initials: M
authors.lastname: Ralston
authors.forename: Clinton
authors.initials: C
authors.lastname: Elfers
authors.forename: Kayoko
authors.initials: K
authors.lastname: Ogimoto
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Kaiyala
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Morton
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000473:pathology; D001835:Body Weight; D002648:Child; D003397:Craniopharyngioma / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism / Q000473:pathology; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D006706:Homeostasis; D006801:Humans; D007029:Hypothalamic Neoplasms / Q000150:complications* / Q000473:pathology; D007031:Hypothalamus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000209:etiology*; D010911:Pituitary Neoplasms / Q000150:complications* / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012970:Sodium Glutamate / Q000009:adverse effects; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism / Q000473:pathology
chemical_list: D012970:Sodium Glutamate